Alopecia Areata: a Comprehensive Review of Pathogenesis and Management

Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis. A meta-analysis of published trials on treatment of alopecia areata states that only few treatments have been well evaluated in randomized trials. Nevertheless, depending on patient age, affected surface area and disease duration, an empiric treatment algorithm can be designed with corticosteroids and topical immunotherapy remaining the mainstay of therapy. The obviously limited success of evidence-based therapies points to a more important complexity of hair loss. At the same time, the complexity of pathogenesis offers opportunities for the development of novel targeted therapies. New treatment opportunities based on the results of genome-wide association studies that implicate T cell and natural killer cell activation pathways are paving the way to new approaches in future clinical trials. Currently, there are ongoing studies with the CTLA4-Ig fusion protein abatacept, anti-IL15Rβ monoclonal antibodies and the Janus kinase inhibitors tofacitinib, ruxolitinib and baricitinib. Ultimately, the options available for adapting to the disease rather than treating it in an effort to cure may also be taken into consideration in selected cases of long-standing or recurrent small spot disease.